Burnt‐Out <scp>MASLD</scp> Predicts Outcomes After Curative Resection for Hepatocellular Carcinoma
BACKGROUND AND AIMS: Hepatic steatosis often diminishes as metabolic dysfunction-associated steatotic liver disease (MASLD) progresses, leading to a so-called 'burnt-out' state. Whether this phenotype simply reflects advanced liver injury or represents a biologically distinct condition with prognostic relevance after hepatocellular carcinoma (HCC) development remains unclear. We evaluated the clinical significance of burnt-out MASLD in patients undergoing curative resection for MASLD-related HCC. METHODS: In this retrospective, pathology-confirmed cohort of patients who underwent curative-intent hepatectomy for MASLD-related HCC (n = 931), concurrent histologic assessment of steatosis (S) and fibrosis (F) was used to define four phenotypes: S > 1/F < 3, S ≤ 1/F < 3, S > 1/F ≥ 3 and burnt-out MASLD (S ≤ 1/F ≥ 3). Postoperative complications, recurrence-free survival and overall survival were evaluated using multivariable Cox proportional hazards models. Paired pathologic reassessment was performed in patients undergoing repeat resection for recurrent HCC. RESULTS: Burnt-out MASLD exhibited the most adverse oncologic phenotype. Relative to the reference phenotype (S > 1/F < 3), burnt-out MASLD was not associated with increased perioperative morbidity but was independently associated with a higher recurrence risk (HR 1.87, 95% CI 1.10-3.17; p = 0.020) and markedly reduced overall survival (HR 3.38, 95% CI 1.57-7.28; p = 0.002). In contrast, steatosis loss without advanced fibrosis and advanced fibrosis with preserved steatosis were not independently associated with recurrence. Paired histologic analysis (n = 39) demonstrated relative stability of steatosis after tumour development, whereas fibrosis progression was observed in a substantial subset. CONCLUSIONS: Burnt-out MASLD represents a distinct histologic phenotype prognostically relevant after curative resection for HCC. Recognition of this entity may refine postoperative risk stratification and inform surveillance strategies in MASLD-related HCC.
Authors
- Katsuya Okada (ORCID: https://orcid.org/0000-0001-9713-0546)
- Yumiko Kageyama (ORCID: https://orcid.org/0000-0002-2398-8723)
- Kenichiro Takase
- Hiroaki Ono (ORCID: https://orcid.org/0000-0001-9230-5714)
- Kojun Okamoto
- Takuya Oba
- Yoshiki Murase
- Masayasu Aikawa
- Isamu Koyama
- Yukihiro Watanabe (ORCID: https://orcid.org/0000-0003-3385-4697)
- Yuichiro Watanabe
Institutions
- Saitama Medical University (JP)
Publication Details
- Journal
- Liver International
- Published
- 2026-05-29
- DOI
- https://doi.org/10.1111/liv.70718
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00